Inspection of pharmaceutical-type product in the operations area is primarily focused on container and closure defects and particulate matter in the product. Both types of defects present potential harm to a patient and the circumstances surrounding their detection and rejection as commercially acceptable are different. Most container and closure defects are easier to detect than particulate matter in a pharmaceutical-type product. Guidance provided by the Parenteral Drug Association (PDA) and the U.S. Food and Drug Administration (FDA) has enabled the creation of clearly defined acceptance criteria and disposition for each type of container and closure defect. On Aug. 1, 2014, the United States Pharmacopeia (USP) released an inspection program as described in Chapter 790, hereby incorporated by reference in its entirety, for detection of particulate matter for products that are injectable for parenteral administration.
Regulations require pharmaceutical-type products intended for injection or ophthalmic use to be sterile and free of particles that could harm a patient. With respect to sterile drug products, only microbial assays can confirm sterility of the drug products. With respect to the drug products being free of particles that could harm a patient, this standard is met by incorporating two Regulatory particulate matter determination methods. The first determination method is in accordance with USP Chapter 790, which requires 100% inspection of every drug container in the lot and the removal of any defective units containing visible size particles, before the batch is released for patient use and is deemed commercially acceptable. For example, Chapter 790 of the USP sets forth the expectation for injectable and ophthalmic products to be “essentially free” of visible particulate matter. This expectation, however, is based on human visual acuity, which is subjective and can be affected by many variables. The second determination method is in accordance with testing methodology and acceptance criteria for sub-visible particles in USP Chapters 788, 789 and 1788.